行動薬理
Behavioral Pharmacology
P3-1-236
オピオイド受容体遮断薬による覚せい剤誘発常同行動の抑制
Opioid receptor antagonists attenuate methamphetamine-induced stereotypical behavior in mice

○北中純一1, 北中順惠1澤井龍生1, 福島侑子1, 田中康一3, 西山信好3, 竹村基彦1
○Junichi Kitanaka1, Nobue Kitanaka1, F. Scott Hall2, George R. Uhl2, Tatsuo Sawai1, Yuko Fukushima1, Koh-ichi Tanaka3, Nobuyoshi Nishiyama3, Motohiko Takemura1
兵庫医大・薬理1, 兵庫医療大・薬・薬理3
Dept Pharmacol, Hyogo Col Med, Nishinomiya, Hyogo, Japan1, Mol Neurobiol, NIDA-IRP, Baltimore, USA2, Div Pharmacol, Dept Pharm, Sch Pharm, Hyogo Univ Hlth Sci, Kobe, Hyogo, Japan3

We investigated the effect of pretreatment with opioid receptor antagonists on methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly inhibited total incidence of METH-induced stereotypical behavior compared with vehicle-pretreated subjects. Mice administered with naloxone and METH showed hyperlocomotion instead of stereotypy. The selective mu opioid receptor antagonist beta-funaltrexamine, but not naltrindole (delta-selective antagonist) or nor-binaltorphimine (kappa-selective antagonist), mimicked the naloxone effect. These observations suggest that the selective mu opioid receptor antagonists inhibit METH-induced stereotypical behavior in mice.
P3-1-237
STX1A、STX1B欠損マウスにおける行動異常の比較
STX1A and STX1B knockout mice exhibited autistic disorder and schizophrenia like neuropsychological abnormalities, respectively

○藤原智徳1, 小藤剛史2, 三嶋竜弥1, 赤川公朗1
○Tomonori Fujiwara1, Takefumi Kofuji2, Tatsuya Misima1, Kimio Akagawa1
杏林大学医学部細胞生理学1, 杏林大学医学部RI部門2
Dept Cell Physiol, Kyorin Univ Sch of Med, Tokyo1, Radio Isotope Lab, Kyorin Univ Sch of Med, Tokyo2

Syntaxin has been thought to regulate vesicle exocytosis. In neurons, highly homologous two types of syntaxin isoform, HPC-1/syntaxin1A (STX1A) and syntaxin1B (STX1B) both of which are transcribed from distinct genes and believed to have similar function, are predominantly expressed. Previously, we generated the gene knockout mice for STX1A or STX1B. Interestingly, STX1A null mutant mice normally developed, but STX1B null mutant mice were dead after birth. In cultured neurons derived from STX1A null mutant, monoamines release was reduced, but Glu and GABA release was normal. In contrast, cultured neurons derived from STX1B null mutant showed reduction of Glu and GABA release, but monoamines release was normal. These results suggested that STX1A and STX1B might have distinct roles in vivo.
In this study, we analyzed the behavioral profiles of the gene knockout mice for STX1A or STX1B in detail. STX1A homozygous and heterozygous mutant mice exhibited attenuation of latent inhibition (LI) which improved by administration of 5HT reuptake inhibitor, and impairment of social cognition which improved by administration of DA reuptake inhibitor or NE reuptake inhibitor. STX1B heterozygous mutant mice exhibited attenuation of LI which improved by administration of 5HT reuptake inhibitor, and impairment of pre-pulse inhibition (PPI) which improved by administration of DA receptor blocker. These observations suggested that lack of STX1A or STX1B induce autistic disorder and schizophrenia like neuropsychological abnormalities, respectively. Implication of these abnormalities in each mutant mouse will be discussed.
P3-1-238
モルヒネ単回投与によるマウスのY字迷路タスク障害
A single administration of morphine impairs Y-maze task in mice

○北中順惠1, 北中純一1, 五藤亜希子1, 三林聡子1, 寛田佑介1, 村西佑美1, 田中康一2, 西山信好2, 竹村基彦1
○Nobue Kitanaka1, Junichi Kitanaka1, Akiko Goto1, Satoko Mibayashi1, Yusuke Kanda1, Yumi Muranishi1, Koh-ichi Tanaka2, Nobuyoshi Nishiyama2, Motohiko Takemura1
兵庫医大・薬理1, 兵庫医療大・薬・薬理2
Dept Pharmacol, Hyogo Col Med, Nishinomiya, Hyogo, Japan1, Div Pharmacol, Dept Pharm, Sch Pharm, Hyogo Univ Hlth Sci, Kobe, Hyogo, Japan2

Chronic opiate treatment causes cognitive deficits, which is considered to be associated with behavioral abnormalities of opiate addiction. We examined the effects of acute morphine on spatial memory, novel object recognition, and state of mood in mice in order to determine whether acute morphine treatment impairs spatial memory. Exposure of ICR male mice to a single dose of morphine significantly reduced alternation behavior in a Y-maze. The reduction was completely recovered by treatment with naloxone. A single morphine treatment significantly attenuated novel objection recognition, which was partially recovered by naloxone. While single morphine treatment did not affect behaviors observed in mice exposed to an elevated-plus maze, a significant reduction in marble-burying behavior was observed compared with vehicle-treated mice. These observations suggest that a single morphine treatment impairs spatial memory in mice via an opioid receptor-mediated mechanism. This may be caused, in part, by a reduced inquisitive behavior (i.e. curiosity-like emotion) to a novel, anxiogenic environment to which mice were exposed.
P3-1-239
マウスの攻撃行動を半自動的に評価する新技術
A novel semi-automated method for measurement of aggressive behavior in mice

○口岩俊子1, 口岩聡2, 村上理3, 三浦可恵1
○Toshiko Kuchiiwa1, Satoshi Kuchiiwa2, Osamu Murakami3, Kae Miura1
鹿児島純心女子大学大学院人間科学研究科心理臨床学1, 鹿児島大学2, 室町機械株式会社3
Dept Clinic Psychol, Grad Sch Human Sci, Kagoshima Immaculate Heart Univ., Satsuma-Sendai,Japan1, Dept. Neuroanatomy, Grad. Sch. Med. Dent. Sci., Kagoshima Univ., Kagoshima, Japan2, Muromachi Kikai Co., Ltd., Tokyo, Japan3

Behavioral assessment of aggressiveness is essential for the analysis of aggression mechanisms and the evaluation of psychotropic drug actions. Current behavioral tests of aggressiveness are usually conducted using a pair of male animals. However, they are generally time-consuming, may vary in terms of the results in each partner, and the results may depend on the subjectivity of the experimenters. Thus, we developed a semi-automated apparatus (TRM) for evaluation of aggressive behavior in mice without a partner. The TRM consists of a mechanical touch stimulator and an aggressive response detector. It is loaded with computer-controlled sticks to give touch stimulations to a mouse and a load sensor to detect the biting responses to the sticks. To evaluate the capacity and reliability of the TRM, changes of biting behavior were assessed using isolation-reared mice. Mice were isolation-reared or group-housed for 7 weeks after weaning and then the isolated mice were re-socialized for additional two weeks. In the isolated group, the biting behavior increased after 1 week from the beginning of isolation, and the responses significantly increased during 7 weeks of isolation-rearing in a time-dependent fashion. The responses decreased significantly throughout the 2 weeks of re-socialization in a time-dependent manner. Other mice isolated for 7 weeks were tested for aggressiveness in both TRM and resident-intruder test, and then buspirone was administered. Buspirone significantly inhibited aggressive behavior in both tests in the same manner. In other mice isolated for over 10 weeks, biting behavior was measured 8 times with a 3- or 4-day interval for 3.5 weeks. The biting behavior was not significantly altered during the experimental periods. These results suggest that the TRM is useful for the quantification of aggressiveness using the same individual repeatedly for a long time, and it is useful for objective evaluation of the effects of a drug on aggressiveness.
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